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FIZZ1 Promotes Airway Remodeling in Asthma Through the PTEN Signaling Pathway

FIZZ1 Promotes Airway Remodeling in Asthma

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Abstract

The aim of our study was to elucidate the function and signaling pathway of found in inflammatory zone 1 (FIZZ1) in airway remodeling in asthma. We used a mice model sensitized and challenged by ovalbumin (OVA) to evaluate the expression of FIZZ1, type I collagen, and fibronectin-1 in the airway in asthma. To investigate the signaling pathway regulated by FIZZ1, we treated a cultured murine lung epithelium cell-12 (MLE-12) with FIZZ1 recombination protein, silenced the expression of FIZZ1 with FIZZ1-shRNA in vitro, and then detected phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and expression of type I collagen and fibronectin-1 (FN-1) by Western blotting. In addition, we increased the expression of PTEN by PTEN plasmid transfection then detected the expression of type I collagen and fibronectin-1 in MLE-12 by Western blot analysis and immunofluorescence cytochemistry technology, respectively. First, the expression of FIZZ1, type I collagen, and fibronectin-1 was significantly elevated in the lungs of OVA-challenged mice compared with saline-treated control animals. Secondly, the phosphorylation of PTEN was decreased in MLE-12 treated with FIZZ1 recombination protein in vitro. On the contrary, the phosphorylation of PTEN was increased in MLE-12 cells transfected with FIZZ1-shRNA. Thirdly, results of the Western blot analysis and immunofluorescence cytochemistry showed that expression of type I collagen and fibronectin-1 was increased in cells treated with FIZZ1 recombination protein, while the levels of type I collagen and fibronectin-1 were significantly decreased in cells transfected with PTEN plasmid. FIZZ1 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting FIZZ1 and/or PTEN may be a new therapeutic strategy for asthma.

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Acknowledgments

We thank Prof. Wenxiang Bi (Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University) for the excellent technical assistance and Yan Wang for providing us with the histochemistry staining apparatus and technical guidance. This work was supported by grants from the Natural and Science Foundation of China (Grant No. 81070016, 81270072).

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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    Authors and Affiliations

    1. Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China

      Jiping Zhao, Xingai Jiao, Jinxiang Wu, Junfei Wang, Wenbin Gong & Liang Dong

    2. Department of Pulmonary Medicine, Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China

      Fen Liu

    3. Department of Pulmonary Medicine, The Second Hospital of Shandong University, Jinan, 250100, People’s Republic of China

      Wen Liu

    4. Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, 250012, People’s Republic of China

      Wenxiang Bi

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    1. Jiping Zhao
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    Correspondence to Liang Dong.

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    Jiping Zhao and Xingai Jiao contributed equally to this work.

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    Zhao, J., Jiao, X., Wu, J. et al. FIZZ1 Promotes Airway Remodeling in Asthma Through the PTEN Signaling Pathway. Inflammation 38, 1464–1472 (2015). https://doi.org/10.1007/s10753-015-0121-5

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